Synthetic Stem Cells Help Repair Damaged Hearts

Stem cell therapies work by secreting factors that help damaged tissue to repair itself, but stem cells are very fragile, hard to store, and can be associated with immune rejection issues and the risk of tumor formation. Scientists in the U.S. and China have now developed synthetic cardiac stem cells that early in vivo tests indicate are as effective as naturally derived human stem cells at helping to promote tissue repair after heart attacks in mice and exhibit none of the most notable drawbacks of naturally derived stem cells. The team, led by Ke Cheng, Ph.D., at the North Carolina State University, suggests that their cell-mimicking microparticles (CMMPs) could represent the foundation for developing off-the-shelf synthetic stem cells for a range of therapeutic indications. The polymer-derived synthetic stem cells are described in Nature Communications in an article entitled “Therapeutic Microparticles Functionalized with Biomimetic Cardiac Stem Cell Membranes and Secretome.”

Professor Cheng’s team constructed the CMMPs from a biodegradable, biocompatible polymer, poly(lactic-co-glycolic acid), or PLGA. They combined the PLGA with growth factors from human cardiac stem cells and coated the particles with cardiac stem cell membrane. Tested in vitro, the CMMPs and human stem cells both promoted the growth of cardiac muscle cells. The artificial stem cells were also as effective as human stem cells at promoting tissue repair in vivo, in a mouse model of cardiac infarction.

The scientists, including colleagues at China’s First Affiliated Hospital of Zhengzhou University, claim that CMMPs are also more robust than human stem cells and can tolerate freezing and thawing. The polymer CMMPs aren’t expected to cause any immunogenicity issues and, because they don’t replicate, will not represent a tumor risk. “The synthetic cells operate much the same way a deactivated vaccine works,” noted Cheng, who is associate professor of molecular biomedical sciences at NC State University, associate professor in the joint biomedical engineering program at NC State, and UNC and adjunct associate professor at the UNC Eshelman School of Pharmacy. “Their membranes allow them to bypass the immune response, bind to cardiac tissue, release the growth factors, and generate repair, but they cannot amplify by themselves. So you get the benefits of stem cell therapy without risks.”

The manufacturing process for the cardiac CMMPs can also be used to generate any type of stem cell, the scientists suggest. “We are hoping that this may be a first step toward a truly off-the-shelf stem cell product that would enable people to receive beneficial stem cell therapies when they're needed, without costly delays,” Professor Cheng concluded.